Improving Early Antibiotic Administration for Treatment of Sepsis at Children’s Hospital of Richmond at VCU: 2012-2019

Background: The Surviving Sepsis Campaign recommends initiating IV antibiotic administration within one hour of recognition of severe sepsis. Several studies have shown that prompt blood culture collection, administration of broad-spectrum antibiotics, and fluid resuscitation following recognition improves child survival. Objective: Our goal was to evaluate effectiveness of sepsis initiatives and institutional changes in the timing of early antibiotic administration at Children’s Hospital of Richmond at VCU. Methods: We formed a Pediatric Sepsis Committee with representatives from each unit in 2013. In 2016, the committee began tracking time from the order of a first stat dose IV antibiotic to administration as a marker of early treatment and reviewed data on a monthly basis with run charts for overall and unit-specific data. Other interventions included improved availability of antibiotics in automated dispensing machines, sepsis screening and alert systems, sepsis huddles, and auto-generated pages to charge nurses upon order of stat IV antibiotics. We included percent of stat antibiotics administered in less than one hour from order across all pediatric units since 2012. Results: Across all units, the centerline of first dose stat antibiotics delivered within one hour improved from a baseline of 34% in 2012 to 76% in 2019. The NICU and PICU centerlines improved by 53% and 48%, respectively since 2012. The Pediatric ED improved from 66% in 2012 to 84% in 2016. The Acute Care Pediatrics (ACP) Unit centerline improved from 24% in 2012 to 50% in 2017. Conclusion: Time from order to stat antibiotic administration has improved in all units receiving quality improvement initiatives. These improvements have been made possible by widespread emphasis on the dangers of untreated sepsis, multidisciplinary collaboration between nursing and physician staff, structural pharmacy changes and electronic alerts. Further studies are needed to determine impact on patient outcomes

Forcespun polyvinylpyrrolidone/copper and polyethylene oxide/copper composite fibers and their use as antibacterial agents

Copper nanoparticles (CuNPs) embedded in polyvinylpyrrolidone (PVP) and polyethylene oxide (PEO) fiber-matrices were prepared through centrifugal spinning of PVP/ethanol and PEO/aqueous solutions, respectively. The prime focus of the current study is to investigate the antibacterial activity of composite fibers against Escherichia coli (E. coli) and Bacillus cereus (B. cereus) bacteria. During the fiber formation, the centrifugal spinning parameters such as spinneret rotational speed, spinneret to collector distance, and relative humidity were carefully chosen to obtain long and continuous fibers. The structural and morphological analyses of both composite fibers were investigated using scanning electron microscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy, and thermogravimetric analysis. In the antibacterial test, PVP/Cu and PEO/Cu composite fibrous membranes exhibited inhibition efficiency of 99.98% and 99.99% against E. coli and B. cereus bacteria, respectively. Basically, CuNPs were well embedded in the fibrous membrane at the nanoscale level, which facilitated the inhibition of bacterial functions through the inactivation of the chemical structure of the cells. Such an effective antibacterial agent obtained from forcespun composite fibers could be promising candidates for biomedical applications

Salvaging diabetic foot through debridement, pressure alleviation, metabolic control, and antibiotics

ABSTRACT There is a fatalist perception of diabetic foot because the argument of ''small-vessel disease'' prevails. This is the report of a cohort study of patients facing a formal recommendation for major foot amputation to assess how many can be saved with a conventional treatment, defined as debridement, pressure alleviation, metabolic control, and antibiotics. The primary efficacy measurement was the salvage of the limb at the follow-up visit between 25 and 35 days after the first consultation. The secondary efficacy measurement was the subsequent epithelization of the ulcerative lesions, following patients for up to 270 days. The cohort consisted of 105 type 2 diabetic patients; 87 (83%) had severe lesions. A total of 71 patients (68%) required hospitalization. By the intention-to-treat analysis, 89 patients (85%) avoided major amputation. A total of 88 patients were evaluated for complete epithelization, reaching median success by day 120. Overall, 51 patients (49%) underwent minor amputations. It was concluded that there is a high rate of unnecessary major foot amputations, because a diabetic foot can be salvaged across the continuum of severity when patients receive care in a multidisciplinary wound clinic

Small for gestational age: Case definition & guidelines for data collection, analysis, and presentation of maternal immunisation safety data.

Need for developing case definitions and guidelines for data collection, analysis, and presentation for small for gestational age (SGA) as an adverse event following maternal immunisation Small for gestational age (SGA) fetuses or newborns are those smaller in size than normal for their gestational age, most commonly defined as a weight below the 10th percentile for the gestational age. This classification was originally developed by a 1995 World Health Organization (WHO) expert committee, and the definition is based on a birthweight-for-gestational-age measure compared to a gender-specific reference population [1,2]

Atypical disengagement from faces and its modulation by the control of eye fixation in children with Autism Spectrum Disorder

By using the gap overlap task, we investigated disengagement from faces and objects in children (9–17 years old) with and without autism spectrum disorder (ASD) and its neurophysiological correlates. In typically developing (TD) children, faces elicited larger gap effect, an index of attentional engagement, and larger saccade-related event-related potentials (ERPs), compared to objects. In children with ASD, by contrast, neither gap effect nor ERPs differ between faces and objects. Follow-up experiments demonstrated that instructed fixation on the eyes induces larger gap effect for faces in children with ASD, whereas instructed fixation on the mouth can disrupt larger gap effect in TD children. These results suggest a critical role of eye fixation on attentional engagement to faces in both groups

An introduction to genetic quality in the context of sexual selection

This special issue of Genetica brings together empirical researchers and theoreticians to present the latest on the evolutionary ecology of genetic quality in the context of sexual selection. The work comes from different fields of study including behavioral ecology, quantitative genetics and molecular genetics on a diversity of organisms using different approaches from comparative studies, mathematical modeling, field studies and laboratory experiments. The papers presented in this special issue primarily focus on genetic quality in relation to ( 1) sources of genetic variation, ( 2) polyandry, ( 3) new theoretical developments and ( 4) comprehensive reviews

Physiological lentiviral vectors for the generation of improved CAR-T cells

Anti-CD19 chimeric antigen receptor (CAR)-T cells have achieved impressive outcomes for the treatment of relapsed and refractory B-lineage neoplasms. However, important limitations still remain due to severe adverse events (i.e., cytokine release syndrome and neuroinflammation) and relapse of 40%-50% of the treated patients. Most CAR-T cells are generated using retroviral vectors with strong promoters that lead to high CAR expression levels, tonic signaling, premature exhaustion, and overstimulation, reducing efficacy and increasing side effects. Here, we show that lentiviral vectors (LVs) expressing the transgene through a WAS gene promoter (AW-LVs) closely mimic the T cell receptor (TCR)/CD3 expression kinetic upon stimulation. These AW-LVs can generate improved CAR-T cells as a consequence of their moderate and TCR-like expression profile. Compared with CAR-T cells generated with human elongation factor alpha (EF1 alpha)-driven-LVs, AW-CAR-T cells exhibited lower tonic signaling, higher proportion of naive and stem cell memory T cells, less exhausted phenotype, and milder secretion of tumor necrosis factor alpha (TNF-alpha) and interferon (IFN)-gamma after efficient destruction of CD19(+) lymphoma cells, both in vitro and in vivo. Moreover, we also showed their improved efficiency using an in vitro CD19(+) pancreatic tumor model. We finally demonstrated the feasibility of large-scale manufacturing of AW-CAR-T cells in guanosine monophosphate (GMP)-like conditions. Based on these data, we propose the use of AWLVs for the generation of improved CAR-T products

Drug treatment program patients' hepatitis C virus (HCV) education needs and their use of available HCV education services

BACKGROUND: In spite of the disproportionate prevalence of hepatitis C virus (HCV) infection among drug users, many remain uninformed or misinformed about the virus. Drug treatment programs are important sites of opportunity for providing HCV education to their patients, and many programs do, in fact, offer this education in a variety of formats. Little is known, however, about the level of HCV knowledge among drug treatment program patients, and the extent to which they utilize their programs' HCV education services. METHODS: Using data collected from patients (N = 280) in 14 U.S. drug treatment programs, we compared patients who reported that they never injected drugs (NIDUs) with past or current drug injectors (IDUs) concerning their knowledge about HCV, whether they used HCV education opportunities at their programs, and the facilitators and barriers to doing so. All of the programs were participating in a research project that was developing, implementing, and evaluating a staff training to provide HCV support to patients. RESULTS: Although IDUs scored higher on an HCV knowledge assessment than NIDUs, there were many gaps in HCV knowledge among both groups of patients. To address these knowledge gaps, all of the programs offered at least one form of HCV education: all offered 1:1 sessions with staff, 12 of the programs offered HCV education in a group format, and 11 of the programs offered this education through pamphlets/books. Only 60% of all of the participating patients used any of their programs' HCV education services, but those who did avail themselves of these HCV education opportunities generally assessed them positively. In all, many patients were unaware that HCV education was offered at their programs through individual sessions with staff, group meetings, and books/pamphlets, (42%, 49%, and 46% of the patients, respectively), and 22% were unaware that any HCV education opportunities existed. CONCLUSION: Efforts especially need to focus on ensuring that all drug treatment program patients are made aware of and encouraged to use HCV education services at their programs